Preclinical Assessment of a New Hybrid Compound C11 Efficacy on Neurogenesis and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice

被引:11
作者
Andres-Mach, Marta [1 ]
Szewczyk, Aleksandra [1 ]
Zagaja, Miroslaw [1 ]
Szala-Rycaj, Joanna [1 ]
Lemieszek, Marta Kinga [2 ]
Maj, Maciej [3 ]
Abram, Michal [4 ]
Kaminski, Krzysztof [4 ]
机构
[1] Inst Rural Hlth, Isobolog Anal Lab, Jaczewskiego 2, PL-20090 Lublin, Poland
[2] Inst Rural Hlth, Dept Med Biol, PL-20090 Lublin, Poland
[3] Med Univ Lublin, Dept Biopharm, Chodzki 4A, PL-20090 Lublin, Poland
[4] Jagiellonian Univ Med Coll, Fac Pharm, Dept Med Chem, Med 9, PL-30688 Krakow, Poland
关键词
anticonvulsant; neuroprotection; neurogenesis; pilocarpine; antiepileptic drugs; HIPPOCAMPAL NEUROGENESIS; ANTICONVULSANT ACTIVITY; ANTIEPILEPTIC DRUGS; LEVETIRACETAM; SEIZURES; EPILEPSY; DESIGN; MEMORY; EPILEPTOGENESIS; EXPRESSION;
D O I
10.3390/ijms22063240
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Status epilepticus (SE) is a frequent medical emergency that can lead to a variety of neurological disorders, including cognitive impairment and abnormal neurogenesis. The aim of the presented study was the in vitro evaluation of potential neuroprotective properties of a new pyrrolidine-2,5-dione derivatives compound C11, as well as the in vivo assessment of the impact on the neurogenesis and cognitive functions of C11 and levetiracetam (LEV) after pilocarpine (PILO)-induced SE in mice. The in vitro results indicated a protective effect of C11 (500, 1000, and 2500 ng/mL) on astrocytes under trophic stress conditions in the MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) test. The results obtained from the in vivo studies, where mice 72 h after PILO SE were treated with C11 (20 mg/kg) and LEV (10 mg/kg), indicated markedly beneficial effects of C11 on the improvement of the neurogenesis compared to the PILO control and PILO LEV mice. Moreover, this beneficial effect was reflected in the Morris Water Maze test evaluating the cognitive functions in mice. The in vitro confirmed protective effect of C11 on astrocytes, as well as the in vivo demonstrated beneficial impact on neurogenesis and cognitive functions, strongly indicate the need for further advanced molecular research on this compound to determine the exact neuroprotective mechanism of action of C11.
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页码:1 / 15
页数:15
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